Katharina Wustrau, Germany

Universitiy Medical Center Hamburg-Eppendorf Pediatric Stem Cell Transplantation and Immunology

Presenter of 2 Presentations

E-Poster Discussion Immune dysregulation & autoimmunity

NEUROIMAGING FINDINGS IN CHILDREN WITH HEREDITARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS – REPORT FROM THE GERMAN REFERENCE CENTER

Lecture Time
13:15 - 13:22
Room
Station 1
Date
19.09.2019, Thursday
Session Time
13:15 - 14:20
Presentation Topic
Immune dysregulation & autoimmunity

Abstract

Background and Aims

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterised by prolonged fever, hepatosplenomegaly and pancytopenia. In the hereditary form, patients may develop inflammatory CNS involvement, presenting with meningism, cranial nerve palsies and seizures, resulting in pathological neuroimaging.

Methods

We aimed to identify the most common neuroimaging findings in patients with hereditary HLH, recruited from the HLH94 and HLH2004 studies in Germany, Switzerland, and Austria.

Results

MRI was available for 37 patients (20f, 17m; median age, 1.5yrs [min, 0.1; max, 17.8]). In patients with more than one MRI, the scan with most pathological changes was selected for cross-sectional analysis. Bilateral symmetric cerebellar lesions were most common (41%, A), followed by diffuse central (38%, B), subcortical (36%) as well as periventricular (31%), cortical (31%, C) and focal subcortical (28%, D) lesions. Contrast enhancement (19%, E) and restricted diffusion (15%) were recorded. Two patients presented with imaging findings of “PRES”. Brain atrophy (F) and abnormal myelination were frequently identified and may be treatment-related. Imaging of the spine (5 patients) showed focal hyperintensity on T2w and focal contrast enhancement.pic_mri_neurohlh.png

Conclusions

Neuroimaging in patients with familial HLH is variable and non-specific, but bilateral symmetric cerebellar lesions, if present, are relatively characteristic in the clinical context.

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Poster Display Immune dysregulation & autoimmunity

TOCILIZUMAB STRIKINGLY ABATES INFLAMMATION IN A GIRL WITH SYMPTOMATIC DEFICIENCY OF THE X-LINKED INHIBITOR OF APOPTOSIS (XIAP) WITH EXTREMELY SKEWED X-INACTIVATION

Lecture Time
10:51 - 10:52
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
128
Presentation Topic
Immune dysregulation & autoimmunity

Abstract

Background and Aims

Patients with deficiency of the x-linked inhibitor of apopotosis (XIAP) may present with inflammatory bowel disease (IBD) and predisposition to hemophagocytic lymphohistiocytosis (HLH). Predominant inactivation of the wildtype x-chromosome has been identified as cause of symptomatic x-linked conditions in females. Inflammation-induced reprogramming of Xiap−/− Treg cells can be prevented by blockade of the IL-6 receptor (IL-6R) in mice.

Methods

A girl presented with very early onset IBD, dermatitis, two episodes of immune dysregulation (5/8 HLH criteria) with spontaneous remission, flares of autoinflammation with fever and elevated markers of inflammation. Infliximab, adalimumab and anakinra only resulted in limited short time effect on IBD and stool-frequency up to 10 times per day, still requiring frequent hospitalization. The introduction of the humanized monoclonal interleukin-6 (IL-6) antibody tocilizumab resulted in absence of fever, resolution of dermatitis, decrease of stool-frequency to 3 times per day, normal activity level, and substantial reduction of corticosteroids.

Results

Diagnosis of XIAP deficiency was established by strongly reduced expression of XIAP in peripheral blood mononuclear cells assessed by flow cytometry. Sanger sequencing of the corresponding gene BIRC4 identified a heterozygous nonsense mutation (c.664C>T; p.Arg222*). An extremely skewed x-inactivation with wildtype inactivation nearly 100% of cells was revealed by HUMARA assay. Introducing the IL-6 antibody tocilizumab lead to substantial reduction of inflammatory activity. SCT from a matched unrelated donor as curative treatment is planned.

Conclusions

Tocilizumab may be considered as treatment alternative in children with XIAP-deficiency. It may help to reduce inflammation and IBD symptoms.

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